KR100654626B1 - Cellulose hard capsule enhancing mechanical film strength - Google Patents

Abstract

The present invention provides a method for producing a cellulose hard capsule, wherein the sucrose fatty acid ester and potassium chloride are added to the aqueous solution of cellulose, and then the mixture is added to the mixture with carrageenan and agar to adjust the viscosity while standing. The cellulose hard capsule of the present invention has an effect of reducing the defects generated during the manufacturing operation and the filling defect generated during the filling operation by improving the mechanical film strength of the capsule.

Cellulose, sucrose fatty acid ester, potassium chloride, carrageenan, agar, hard capsule

Description

Cellulose hard capsule enhancing mechanical film strength

1 is a view showing a method and apparatus for measuring the mechanical film strength of the cellulose hard capsule of the present invention. Lower the measuring rod and press 4mm from the moment the capsule is in contact to measure the strength.

The present invention relates to an improved cellulose hard capsule prepared by adding a polymer polysaccharide to a cellulose substrate and a method for producing the same. More specifically, the present invention relates to a cellulose hard capsule having improved mechanical film strength and a method for producing the same, which are prepared by adding sucrose fatty acid ester and potassium chloride to a cellulose aqueous solution base and mixing and drying carrageenan and agar mixed solution as a gelling agent.

Cellulose hard capsules have a water content of less than 10%, which is lower than gelatine hard capsules, so it is suitable for filling moisture-sensitive hygroscopic preparations, and there is no problem of protein denaturation or BSE problems in gelatin. Because of its origin, it has utility as a light hard capsule formulation useful for vegetarians who avoid animal nature for religious reasons.

On the other hand, cellulose hard capsules are difficult to commercialize due to the lack of stability due to the strength of the product and the change over time due to insufficient gelation in aqueous solution compared to gelatin hard capsules. In order to enhance the gelling action of such cellulose hard capsules, some methods of preparing cellulose hard capsules by adding various polymer polysaccharides are known.

U.S. Patent No. 5,431,917 discloses a cellulose hard capsule which may contain a medicament.At this time, potassium ions, ammonium ions or calcium ions are added to the base of the cellulose aqueous solution by adding carageenan as a gelling agent and as a gelling aid. After gelling and then molding through a molding pin to disclose a method for producing a cellulose hard capsule.

On the other hand, US Patent No. 6,517,865 B2 discloses 0.01-5% by weight of gellan gum, 0.01-8% by weight of ethylenediaminetetraacetic acid (EDTA), citric acid in 90-99.98% by weight of at least one cellulose ether. A polymer film composition for cellulose capsules comprising sodium, citric acid and mixtures thereof as a requesting agent is disclosed.

In addition, the present inventors also prepared a mixed solution by adding a mixed solution of pectin and glycerin to an aqueous solution of cellulose in US Patent No. 6,410,050 B1, and then adding glacial acetic acid, calcium gluconate, sucrose fatty acid ester, and the like to adjust the viscosity to cellulose capsules. The method for molding the cellulose capsules prepared by the above method has been disclosed.

However, cellulose hard capsules prepared by the above methods also have disadvantages of low strength and high oxygen permeability of the capsule's mechanical coating as compared to gelatin hard capsules. The reason why the mechanical strength of the cellulose hard capsule is low is a problem due to the physical properties of the cellulose itself, which causes the following problems during product manufacturing and filling.

First, when a capsule is separately formed into a cap part and a body part in a capsule maker, when a joint part is joined to each other in a joiner block, a joint defect is generated a lot due to low mechanical film strength.

Second, in the process of transferring capsule between drum and drum in capsule appearance inspection machine, capsule printing machine, capsule filling machine, mechanical film strength is low, so many defects occur due to pinched or pressed in drum.

Third, in order to transfer the printing ink deposited on the rubber roll to the capsule surface during the spin printing operation while rotating the capsule, the rubber roll must press the capsule with an appropriate force, but at this time, the mechanical film strength is low, so that a lot of distortion is generated.

Fourth, the capsule is separated into a cap part and a body part during the filling operation of the capsule, and after filling a certain amount of filler in the body part, the cap part and the body part are combined again. At this time, the mechanical film strength is low, which causes a lot of telescope defects. .

Therefore, the present invention has been found to improve the film strength of the cellulose hard capsules when adding a specific polymer polysaccharide during the development of the composition of the hard cellulose hard capsules that can improve the mechanical film strength and completed the present invention.

The technical problem to be achieved by the present invention is to develop a film composition that can improve the mechanical film strength of the cellulose hard capsules through a change in the composition of the aqueous solution of cellulose, a defect that occurs during manufacturing, such as bonding failure, crushing, telescope The present invention seeks to develop a hardened cellulose hard capsule and a method for producing the same, which reduces mechanical film strength.

An object of the present invention is to add a sucrose fatty acid ester and potassium chloride to the aqueous solution of cellulose, and then to add a mixture of carrageenan and agar mixed solution to the mixture solution to provide a method for producing a hard cellulose hard capsules characterized in that the viscosity is controlled and molded will be.

Further, 0.1 to 0.5 parts by weight of sucrose fatty acid ester and 0.05 to 0.3 parts by weight of potassium chloride were added to 100 parts by weight of an aqueous solution of cellulose containing 18 to 21 parts by weight of cellulose, and then 0.1 to 1.0 parts by weight of carrageenan and 0.02 to 0.5 parts by weight of agar. It is characterized by adjusting and molding the viscosity while mixing and adding the compounding solution.

On the other hand, the weight ratio of the carrageenan and agar compound solution is 2.5 to 3.5: 1, characterized in that the cellulose is hydroxypropyl methyl cellulose (HPMC).

In another aspect, the present invention provides a cellulose hard capsule prepared according to the above method, wherein the hard capsule is 100 parts by weight of cellulose, 0.5 to 2.5 parts by weight of sucrose fatty acid ester, 0.2 to 1.5 parts by weight of potassium chloride, 0.5 to 5.0 parts by weight of carrageenan And 0.1 to 2.5 parts by weight of agar.

Hereinafter, the present invention will be described in more detail.

In order to manufacture a cellulose capsule, a method of depositing and gelling an aqueous solution of cellulose on a molding pin includes a physical manufacturing method and a chemical manufacturing method.

The physical manufacturing method is to gel the deposited aqueous solution by heat by raising the temperature of the forming pin to a high temperature (about 67 ° C), and the chemical manufacturing method is to gel by adding polysaccharides to the aqueous solution of cellulose.

Of these two methods, the mechanical film strength of the capsule produced by the physical method shows a higher mechanical film strength than that of the capsule manufactured by the chemical method, but it can be seen that the mechanical film strength is lower than that of the gelatin capsule. Table 1 is a chart comparing the mechanical film strength of cellulose hard capsules according to the manufacturing method and the mechanical film strength of gelatin hard capsules.

Comparative Table of Mechanical Coating Strength between Gelatin Hard Capsule and Cellulose Hard Capsule division Film strength measurement result (g) maximum Average at least Gelatin Hard Capsule 561 468 417 Cellulose Hard Capsule    Physical gelation method 448 356 290 Chemical gelation method pectin 292 234 200 Gellan gum 343 300 276 Carrageenan 382 338 280

The measuring instrument used was Texture Analyser (Model TA 1000), measuring rod descending speed was 0.5mm / sec, measuring depth was 4mm, and the measuring method was to place # 0 capsule horizontally on the Texture Analyser and lower the measuring rod. The strength is measured by pressing 4 mm from the moment of contact with the capsule.

As shown in Table 1, although the chemical manufacturing method in the cellulose hard capsule manufacturing method is lower than the mechanical manufacturing method, the mechanical film strength is nevertheless, the reason why most capsule manufacturers use the chemical manufacturing method is that the conventional manufacturing method is hard This is because there is no cost burden to modify the molding pins used in capsule manufacturing machines or deposition, but the chemical manufacturing method does not have to modify the molding pins or manufacturing machines.

However, since the mechanical film strength of the hard capsule manufactured by the chemical method is much lower than that of the gelatin hard capsule, the mechanical film strength is relatively high in the chemical manufacturing method as shown in Table 1 to improve the problems caused by such a decrease in mechanical film strength. After selecting a high carrageenan and another polysaccharide to make a blended solution to prepare a capsule and tested whether the mechanical film strength is improved.

The polysaccharides used were agar gum, guar gum, locust bean gum, gellan gum, xanthan gum, pectin, starch, furcelleran , Polysaccharides such as furluran, agar, and one or several combinations with carrageenan to make a mixed solution.

As a result, the desired mechanical coating strength was improved when agar and carrageenan were combined with these polysaccharides, and the film distribution of the coating became more homogeneous when sucrose fatty acid ester was added thereto. there was.

It will be described in more detail through the following examples and comparative examples that the composition of the present invention has improved mechanical film strength.

Preparation Examples 1 to 5 Preparation of Cellulose Hard Capsule

To prepare a cellulose hard capsule in the composition of Table 2. As shown in Table 2 below, the content of carrageenan and agar was changed on the cellulose substrate, and the amounts of sucrose fatty acid ester and potassium chloride were consistent.

Ingredient Preparation Example 1 Preparation Example 2 Preparation Example 3 Preparation Example 4 Preparation Example 5 HPMC 86.666 86.666 86.666 86.666 86.666 Sucrose Fatty Acid Ester  4.444  4.444  4.444  4.444  4.444 Potassium chloride  2.222  2.222  2.222  2.222  2.222 Carrageenan  4.666  5.000  5.333  6.000  6.333 Agar  2.000  1.666  1.333  0.666  0.333

Example 1 Measurement of Mechanical Strength of Cellulose Hard Capsule Film

Table 5 shows the results of measuring the mechanical strength of the film using five # 0 capsules prepared in Production Examples 1 to 5.

Comparison table of mechanical strength of film (n: 100) division Preparation Example 1 Preparation Example 2 Preparation Example 3 Preparation Example 4 Preparation Example 5 Gelatin Hard Capsule Mechanical strength of film (g) maximum 468 452 421 415 396 561 Average 413 405 370 360 340 468 at least 380 364 345 320 294 417

* The measuring method of film mechanical strength is the same as that of Table 1.

As shown in the above manufacturing example, the composition ratio of carrageenan was gradually decreased and the composition ratio of agar was gradually increased. In Production Examples 1, 2, and 3, the gelling power was improved, the structure of the coating was strengthened, and the strength was higher than that of the hard capsule produced by the physical manufacturing method.

However, in the case of Preparation Example 1, the mechanical strength of the capsule showed the highest value, but the drawback was that the transparency of the capsule coating was lower than that of the conventional cellulose hard capsule.

Example 2 Cellulose Hard Capsule Film Transparency Measurement

Comparative results of the transparency of the cellulose hard capsule film prepared in Preparation Examples 1 to 5 are shown in Table 4.

The measuring instrument used was a UV-visible spectrometer, and the measuring method was to cut the body portion of the hard capsule into 1 cm width and 1 cm length and measure transparency at 570 nm of the UV meter with this film.

Transparency comparison table of film division Preparation Example 1 Preparation Example 2 Preparation Example 3 Preparation Example 4 Preparation Example 5 Gelatin Capsule  Transparency (%) 45% 54% 57% 59% 63% 53%

Therefore, Preparation Example 2 is suitable for the composition ratio in which the film strength is close to the film strength of the gelatin hard capsule without affecting the transparency of the film.

Example 3 Preparation of Cellulose Hard Capsule of the Present Invention

19.5Kg of hydroxypropylmethylcellulose (concentration: 19.5%) was added and dispersed in 79.915L of purified water at 80 ° C, and 195g of sucrose fatty acid ester (concentration: 0.195%) and 97.5g of potassium chloride (concentration: 0.097%) were weighed. Thereafter, 219.375 g of carrageenan (concentration: 0.219%) and 73.125 g of agar (concentration: 0.073%) were prepared and weighed, and then stirred slowly at 60 rpm for 2 hours to prepare an aqueous solution. After stirring is complete, the aqueous solution temperature of about 80 ° C. is cooled to about 45 ° C., which is the dissolution temperature, and then the temperature of the aqueous solution is raised to about 58 ° C., which is the deposition molding temperature. Capsules were made.

Example 4 Comparative Test of Fillability of Cellulose Hard Capsule of the Present Invention

Prepared by the method described in Example 3, and the # 0 transparent hard capsules were deposited by this method, and compared with the cellulose hard capsules using the conventional pectin disclosed in US Patent No. 6,410,050 B1 and the filling properties were compared and tested. 5 is shown.

Fillability comparison table Charger mode EXC-100F Charge rate 50,000 pcs / hour 100,000 pcs / hour Vacuum 20cmHg 20cmHg Filling quantity 500,000 500,000 Charging result division Counterpart Invention Counterpart Invention Telescope 15 One 20 3 Distortion 8 0 10 One

As shown in the comparative table of Table 5, as the strength of the coating of the present invention prepared in Example 3 is improved, excellent filling results in which telescopes and crushing defects are generated very little during filling are obtained.

Example 5 Comparative Test of Printability of Cellulose Hard Capsule of the Present Invention

Prepared by the method described in Example 3, and # # # transparent hard capsules were deposited by this method to compare the printability and cellulose hard capsules using a conventional pectin and the results are shown in Table 6.

Printability Comparison Table Printing machine mode EXC-100R (Spin Printer) Printing speed 100,000 / hour Print quantity 500,000 Distortion defect quantity Counterpart Invention 10 things One

As shown in the printability comparison table of Table 6, as the strength of the film of the present invention prepared in Example 3 is improved, excellent printing results are obtained in which very little distortion occurs during printing.

Example 7 Roundness Comparison Test of Cellulose Hard Capsule of the Present Invention

Prepared by the method described in Example 3, and # # # transparent hard capsules were deposited by this method to compare the cellulose hard capsules using a conventional pectin and roundness and the results are shown in Table 7.

Roundness comparison table (n: 50) division Counterpart Invention Roundness (%) cap body cap body 98.3% 98.5% 99.3% 99.5%

The measuring device used was a profile projector, and the measuring method was to divide the size 0 hard capsule into a cap and a body, and measure the roundness by measuring the outer diameters of the X and Y axes of the capsule cut surface in the profile projector.

As shown in the roundness comparison table of Table 7, the roundness of the capsule was greatly improved as the strength of the film of the present invention prepared in Example 3 was improved.

The effect of the present invention is that the mechanical strength of the film of the cellulose hard capsule is much lower than that of the gelatin hard capsule, in order to improve the mechanical film strength of the cellulose hard capsule to improve the defects and troubles caused by the problem of strength degradation during manufacturing or filling. Addition experiments were performed by combining various polysaccharides, and when the proper amount of agar was added to carrageenan, the mechanical film strength of the desired capsule was increased, and cellulose hard capsules having the above composition were produced. It has contributed greatly to productivity improvement by eliminating defects and troubles.

Claims (6)

0.1 to 0.5 parts by weight of sucrose fatty acid ester and 0.05 to 0.3 parts by weight of potassium chloride were added to 100 parts by weight of an aqueous solution of cellulose containing 18 to 21 parts by weight of cellulose, and then 0.1 to 1.0 parts by weight of carrageenan and 0.02 to 0.5 parts by weight of agar were added to the mixture. Method for producing cellulose hard capsules characterized in that the solution is mixed and added, and then molded delete The method of claim 1, wherein the weight ratio of carrageenan and agar compound solution is 2.5 to 3.5: 1. According to claim 1, wherein the cellulose is hydroxypropyl methyl cellulose (HPMC) method for producing a hard cellulose hard capsules, characterized in that Cellulose hard capsule prepared according to the method of claim 1 The cellulose hard capsule according to claim 5, which contains 100 parts by weight of cellulose, 0.5 to 2.5 parts by weight of sucrose fatty acid ester, 0.2 to 1.5 parts by weight of potassium chloride, 0.5 to 5.0 parts by weight of carrageenan, and 0.1 to 2.5 parts by weight of agar.

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